Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215000, Jiangsu Province, China; Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), No.2 Zheshan Road, Wuhu, 241001, Anhui Province, China.
Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215000, Jiangsu Province, China.
Biochem Biophys Res Commun. 2022 May 14;604:158-164. doi: 10.1016/j.bbrc.2022.03.045. Epub 2022 Mar 11.
Angiogenesis is a key physiological process that plays a key role in glioblastoma (GBM) progression and displays therapeutic resistance to antiangiogenic therapies. In this study, we aimed to identify whether vascular endothelial growth factor receptor 2(VEGFR2)monoclonal antibodies(mab)could inhibit tumorigenicity and the formation of vascular mimicry (VM) in GBM. The bioinformatic analysis from TCGA, CGGA, and TCPA databases and Immunohistochemistry (IHC) revealed that VEGFR2 is highly expressed in glioma tissues and results in a poor prognosis and is positively associated with VM markers (CD34 and PAS). The anti-VEGFR2 monoclonal antibodies(MSB0254)could inhibit the invasion, migration, and VM formation of U251 and primary glioma cells in vitro. In vivo, MSB0254 (m) could not only inhibit the growth of transplanted tumors of U251 and GL261 cells, but also significantly inhibit the expression of CD34, VEGFR2, Ki67, MMP2, MMP9 and reduce the expression of CD34/PAS and inhibit VM formation. The VEGFR2 monoclonal antibody could inhibit the angiogenesis and tumor growth of GBM by blocking the signaling pathway mediated by VEGFR2. It may become a new supplementary treatment for GBM.
血管生成是一种关键的生理过程，在胶质母细胞瘤（GBM）的进展中起着关键作用，并对血管生成抑制剂治疗表现出治疗抵抗。在这项研究中，我们旨在确定血管内皮生长因子受体 2（VEGFR2）单克隆抗体（mab）是否可以抑制 GBM 的致瘤性和血管模拟（VM）的形成。来自 TCGA、CGGA 和 TCPA 数据库的生物信息学分析和免疫组织化学（IHC）显示，VEGFR2 在胶质瘤组织中高度表达，导致预后不良，并且与 VM 标志物（CD34 和 PAS）呈正相关。抗 VEGFR2 单克隆抗体（MSB0254）可以抑制 U251 和原代胶质瘤细胞在体外的侵袭、迁移和 VM 形成。在体内，MSB0254（m）不仅可以抑制 U251 和 GL261 细胞移植瘤的生长，还可以显著抑制 CD34、VEGFR2、Ki67、MMP2、MMP9 的表达，降低 CD34/PAS 的表达，并抑制 VM 的形成。VEGFR2 单克隆抗体通过阻断 VEGFR2 介导的信号通路抑制 GBM 的血管生成和肿瘤生长。它可能成为 GBM 的一种新的辅助治疗方法。
